Polysaccharides Reduce Absorption and Mutagenicity of 3-Amino-1,4-Dimethyl-5H-Pyrido[4,3-b]Indole In Vitro and In Vivo.

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is a group 2B carcinogen characterized by the International Agency for Research on Cancer (IARC) and great efforts have been taken to reduce Trp-P-1 mutagenicity to humans. In this study, the effect of a reduction of Trp-P-1 on intestinal absorption as a promising strategy was investigated. The data showed that when 20 mM Trp-P-1 cotransported with 10 mM of sodium carboxymethyl cellulose (CMC), xanthan gum, or carrageenan, the absorption rate of Trp-P-1 was reduced by 31.5%, 49.5%, or 72.9% in MDCK-MDR1 cell monolayer, respectively; and 64.6%, 83.4%, or 64.1% in rat intestinal tissues, correspondingly. These 3 polysaccharides also reduced pharmacokinetic parameters, that is, Cmax , AUC0-t , and AUC0-∞ , after Trp-P-1 was given to rats intragastrically. However, gum arabic did not exhibit similar effects on Trp-P-1 absorption in vitro or in vivo. The Ames test showed that these 3 polysaccharides reduced Trp-P-1 mutagenicity to Salmonella typhimurium TA98, but gum arabic did not. Isothermal titration calorimetry assay indicated that Trp-P-1 interacted with these 3 polysaccharides. Thermodynamic study showed that the actual value of △H <0, but its absolute value greater than the corresponding value of T∆S, suggest a specific interaction between Trp-P-1 and these 3 polysaccharides, probably through the hydrogen bond and/or ion interaction. Reduction of Trp-P-1 intestinal absorption using food additives could be one of the strategies to suppress Trp-P-1-induced carcinogenesis in human.

PRACTICAL APPLICATION: 1.This study provides insightful information for the food industry how gum arabic, xanthan gum, kappa carrageenan, and sodium carboxymethyl cellulose affect the absorption of Trp-P-1. 2.This study also provides novel information regarding a better formulation for meat products to reduce Trp-P-1 absorption.